Bedaquiline Resistance: A Looming Global Threat in Tuberculosis Management.

The development of bedaquiline holds promise for treating multidrug-resistant tuberculosis (MDR-TB). Still, the inflation in bedaquiline resistance has alarmed the global public health crisis, indicating the need for a new treatment strategy. Several scientific studies have reported a high incidence of resistance among MDR-TB patients who had prior exposure to bedaquiline for treating Mycobacterium tuberculosis infections. Disparate research findings indicate that individuals previously administered this drug exhibit a remarkable prevalence of resistance. Studies have further demonstrated that prior treatment often correlates with the emergence of resistant Mycobacterium tuberculosis strains. Overall, evidence from multiple investigations highlights a concerning trend of increased resistance in MDR-TB cases with a history of bedaquiline therapy. Moreover, bedaquiline resistance in MDR-TB strains has been linked to mutations in several chromosomal genes, including atpE, Rv0677c, Rv0678, and pepQ. Consequently, it is imperative to mitigate the burden of MDR-TB and bedaquiline resistance. Herein, this article emphasizes structural features, mechanism of action, emergence of underlying resistance mechanisms, pharmacokinetic & pharmacodynamic properties, clinical toxicity, and strategies to combat resistance associated with bedaquiline.